title: HLA-driven convergence of HIV-1 viral subtypes B and F toward the adaptation to immune responses in human populations.
abstract: BACKGROUND
  Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1.
  
  
  RESULTS
  We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes.
  
  
  CONCLUSIONS
  Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate.
authors.affiliation: Centro Nacional de Referencia para el SIDA, Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Capital Federal, Buenos Aires, Argentina.
authors.forename: Dario Alberto
authors.initials: DA
authors.lastname: Dilernia
authors.forename: Leandro
authors.initials: L
authors.lastname: Jones
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Rubio
authors.forename: Sandra
authors.initials: S
authors.lastname: Pampuro
authors.forename: Manuel
authors.initials: M
authors.lastname: Gomez-Carrillo
authors.forename: Christian T
authors.initials: CT
authors.lastname: Bautista
authors.forename: Christian
authors.initials: C
authors.lastname: Bautista
authors.forename: Gabriel
authors.initials: G
authors.lastname: Deluchi
authors.forename: Jorge
authors.initials: J
authors.lastname: Benetucci
authors.forename: María Beatriz
authors.initials: MB
authors.lastname: Lasala
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lourtau
authors.forename: Marcelo Horacio
authors.initials: MH
authors.lastname: Losso
authors.forename: Héctor
authors.initials: H
authors.lastname: Perez
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
mesh_terms: D000956:Antigens, Viral / Q000235:genetics; D005075:Biological Evolution; D000939:Epitopes / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007109:Immunity; D015233:Models, Statistical; D009154:Mutation; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D015683:Gene Products, gag; D006680:HLA Antigens; D015235:HLA-B Antigens